American Indian (AI) families now living in urban areas experience disproportional health disparities associated with substance abuse and risky sexual behavior but few evidence-based prevention approaches exist to prevent, reduce and eliminate health disparities among this rapidly growing population. Family disruption, stresses related to poverty and rural-to-urban migration, and loss of cultural and social connections frequently operate as pathways to adverse health outcomes among AI families. By strengthening family functioning (parental involvement, family support, parental monitoring, and parent-child communication), a parenting intervention can help parents strengthen culturally relevant parenting skills that are consistent with promoting their children's health and well-being, and help them serve as direct sources of influence in reducing their children's risk of substance use and risky sexual behavior. The proposed study draws upon the project team's research, conducted at an NCMHD Center of Excellence, on the social determinants of AI families' behavioral health, their salient risk and resiliency factors, culturally appropriate strategies for resisting risk behaviors, and systematic methods for culturally adapting prevention programs. The aims of the study are to create and test a culturally grounded parenting intervention for urban AI families through a modification of an existing prevention program, Families Preparing the Next Generation (FPNG). The adaptation will employ a Cultural Adaptation Model for adapting programs for new target populations in ways that increase cultural fit while maintaining fidelity to core components of the original program. The intervention will be adapted, piloted, evaluated, culturally validated, revised accordingly, and tested in a randomized control trial (RCT) involving 600 families (300 intervention, 300 control) in partnership with the three largest urban Indian centers in Arizona. Ecodevelopmental Theory provides the framework for identifying parental, family, peer, community and cultural influences on youths' substance use and risky sexual behavior. CBPR methods will be used to adapt the intervention, using feedback from focus groups of urban AI parents, AI professionals and prevention experts, and through close collaboration between the designers of the original intervention and staff of the urban Indian centers, thus increasing the capacity of those centers to provide future parenting interventions. In addition to testing the intervention's efficacy, we will assess whether and how the participants' connection to native culture and identity influences the interventions effects, and whether changes in overall family functioning lead to specific parenting practices directed at reducing their children's risk behaviors. These models and theory can inform the design and implementation of more effective, culturally relevant interventions. The resulting prevention intervention will address the needs of an under-served group severely affected by health disparities, strengthen families and help them to avoid familial and individual dysfunction, and advance knowledge on effective translational research strategies for adapting prevention interventions for ethnically diverse families. PUBLIC HEALTH RELEVANCE: The proposed study responds to a need, identified by urban Indian coalitions in Arizona and across the nation, for innovative culturally grounded prevention program adaptation for urban American Indian (AI) families. Public health efforts to address unacceptably high levels of substance use and risky sexual behavior among urban AI youth can be advanced through the creation of an intervention that focuses on effective parenting strategies tailored to the cultural and social forces that urban AI families face. The CBPR methodology of the study not only integrally involves community partners and community members in the design and testing of the intervention, it builds institutional capacity for sustaining the development and delivery of this and similarly designed culturally grounded prevention interventions.